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Evaluation of early and late histamine release by three standard volume substitutes


Following meta-analysis [1], the use of colloidal solutions in intensive care medicine is under discussion. Although polygeline [2] and human albumin are known to cause histamine release, other substances eg hydroxyethyl starch were thought to be without effect. Histamine release depends on the clinical scenario, concomitant drugs, infusion speed, duration and amount of infusion. However, there is no information about their effect regarding time periods longer than immediate reactions. This study investigated the histamine releasing effects of three plasma substitutes administered and observed over a longer period of time, simulating many of the clinical scenarios.


In a prospective, randomised, controlled clinical study 21 healthy, male volunteers were randomly allocated to three groups receiving i.v. 3.5% polygeline (Haemaccel, n = 9), 5% human albumin (n = 6) and 3% hydroxyethyl starch 200/0.5 (HAES-steril, n = 6) for normovolaemic haemodilution over a period of 90 min, after calculated and adjusted blood withdrawal before infusion. H1-antagonist (dimetinden) and H2-antagonist (cimetidine) i.v. premedication was given to prevent histamine-related clinical signs. Blood samples for plasma histamine determination were drawn at defined time points and systemic (cardiovascular, skin reactions, etc) parameters documented over 240 min after start of infusion.


There was a high overall incidence of histamine release in all groups (Haemaccel 100% [9/9], Albumin 100% [6/6], HAES 100% [6/6]). In the first 30 min, histamine release was observed in all groups (Haemaccel 77.8% [7/9], Albumin 50% [3/6], HAES 50% [3/6]; P > 0.05 between groups). Peak values were 4.59 ng/ml (Haemaccel), 3.42 ng/ml (Albumin) and 4.98 ng/ml (HAES). H1 + H2 prophylaxis prevented systemic histamine related symp-toms, although one HAES subject had a histamine associated reaction (headache).


This study demonstrated that infusion of all colloidal plasma substitutes tested is associated with early and late histamine release. This reaction is a known phenomenon for polygeline and albumin, but a novel finding for HAES and should be considered in further routine clinical use.


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Celik, I., Duda, D., Stinner, B. et al. Evaluation of early and late histamine release by three standard volume substitutes. Crit Care 5, P117 (2001).

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  • Histamine
  • Cimetidine
  • Histamine Release
  • Intensive Care Medicine
  • Human Albumin